染色质三维结构与基因调控网络在儿童代谢性疾病中的遗传学机制进展

doi:10.11852/zgetbjzz2025-0302

中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (10): 1082-1085.DOI: 10.11852/zgetbjzz2025-0302

染色质三维结构与基因调控网络在儿童代谢性疾病中的遗传学机制进展

高建芳¹, 单小玉², 郭锡熔¹

1.上海市同仁医院,上海交通大学医学院附属同仁医院内分泌科,上海 200336;
2.蚌埠医科大学生命科学院

收稿日期:2025-03-27 修回日期:2025-06-09 发布日期:2025-10-11
通讯作者: 郭锡熔,E-mail: xrguo@shsmu.edu.cn
作者简介:高建芳(1990—),女,硕士学位,主要研究方向为儿童肥胖和生长发育。
基金资助:
国家重点研发计划(2021YFC2701900, 2021YFC2701903);上海交通大学医学院上海同仁医院科研基金(TRYJ2024LC03);国家自然科学基金(82100915)

Progress in genetic mechanisms of chromatin 3D structure and gene regulatory networks in pediatric metabolic disorders

GAO Jianfang¹, SHAN Xiaoyu², GUO Xirong¹

1. Department of Endocrinology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China;
2. College of Life Sciences, Bengbu Medical University

Received:2025-03-27 Revised:2025-06-09 Published:2025-10-11
Contact: GUO Xirong, E-mail: xrguo@shsmu.edu.cn

摘要/Abstract

摘要： 基因表达不仅由编码序列决定,还受非编码区调控元件的调控。作为关键表观遗传因素,染色质三维结构的动态变化与疾病发生密切相关。三维基因组通过空间构象将远距离的启动子、增强子等顺式调控元件聚集,从而调控胰岛素分泌、脂肪细胞分化及能量代谢等关键通路中的基因表达。本文综述了染色质三维结构的基本特征及其在儿童代谢性疾病中的研究进展,重点探讨其在肥胖、糖尿病和非酒精性脂肪肝等疾病中的调控机制。通过了解染色质三维结构变化和基因调控之间的关系,从而更深入理解儿童代谢性疾病。

关键词: 染色质三维结构, 三维基因组, 基因表达调控, 儿童代谢性疾病, Hi-C技术

Abstract: Gene expression is not solely determined by coding sequences but is also regulated by non-coding cis-regulatory elements.As a key epigenetic factor, the dynamic organization of chromatin in three-dimensional (3D) space plays a critical role in the onset and progression of disease.The 3D genome architecture enables distal cis-regulatory elements, such as promoters and enhancers, to be spatially juxtaposed, thereby orchestrating gene expression in essential metabolic pathways, including insulin secretion, adipocyte differentiation, and energy metabolism.This review summarizes the fundamental characteristics of chromatin 3D structure and highlights recent advances in its role in pediatric metabolic diseases.Particular attention is given to its regulatory mechanisms in obesity, diabetes, and nonalcoholic fatty liver disease.Understanding the interplay between 3D genome organization and gene regulation provides novel insights into the molecular basis of pediatric metabolic diseases.

Key words: chromatin 3D structure, three-dimensional genomics, gene expression regulation, pediatric metabolic diseases, Hi-C

中图分类号:

R179

高建芳, 单小玉, 郭锡熔. 染色质三维结构与基因调控网络在儿童代谢性疾病中的遗传学机制进展[J]. 中国儿童保健杂志, 2025, 33(10): 1082-1085.

GAO Jianfang, SHAN Xiaoyu, GUO Xirong. Progress in genetic mechanisms of chromatin 3D structure and gene regulatory networks in pediatric metabolic disorders[J]. Chinese Journal of Child Health Care, 2025, 33(10): 1082-1085.

参考文献

[1] Kerr JA, Patton GC,Cini KI, et al.Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990-2021, with forecasts to 2050: A forecasting study for the global burden of disease study 2021[J].Lancet, 2025, 405(10481): 785-812.
[2] Huang Y,Sulek K, Stinson SE, et al.Lipid profiling identifies modifiable signatures of cardiometabolic risk in children and adolescents with obesity[J].Nat Med, 2025, 31(1): 294-305.
[3] Ma G, Meyer CL, Jackson-Morris A, et al.The return on investment for the prevention and treatment of childhood and adolescent overweight and obesity in China: A modellingstudy[J].Lancet Reg Health West Pac, 2024, 43: 100977.
[4] Han C, Song Q, Ren Y, et al.Global prevalence of prediabetes in children and adolescents: A systematic review and meta-analysis[J].J Diabetes, 2022, 14(7): 434-441.
[5] Sethi JK, Hotamisligil GS.Metabolic messengers: Tumour necrosis factor[J].Nat Metab, 2021, 3(10): 1302-1312.
[6] Zhou N, Qi H, Liu J, et al.Deubiquitinase OTUD3 regulates metabolism homeostasis in response to nutritional stresses[J].Cell Metab, 2022, 34(7): 1023-1041.
[7] Huang T, Zhuang Z,Heianza Y, et al.Interaction of diet/lifestyle intervention and tcf7l2 genotype on glycemic control and adiposity among overweight or obese adults: Big data from seven randomized controlled trials worldwide[J].Health Data Sci, 2021, 2021: 9897048.
[8] Krumm A, Duan Z.Understanding the 3D genome: Emerging impacts on human disease[J].Semin Cell Dev Biol, 2019, 90: 62-77.
[9] Chew NWS, Ng CH, Tan DJH, et al.The global burden of metabolic disease: Data from 2000 to 2019[J].Cell Metab, 2023, 35(3): 414-428.
[10] Barutcu AR, Lajoie BR, McCord RP, et al.Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells[J].Genome Biol, 2015, 16: 214.
[11] Rao SSP, Huang SC, Glenn StHilaire B, et al.Cohesin loss eliminates all loop domains[J].Cell, 2017, 171(2): 305-320.
[12] Hamagami N, Wu DY, Clemens AW, et al.NSD1 deposits histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons[J].Mol Cell, 2023, 83(9): 1412-1428.
[13] Zabidi MA, Stark A.Regulatory enhancer-core-promoter communication via transcription factors and cofactors[J].Trends Genet, 2016, 32(12): 801-814.
[14] Yan W, Chen D, Schumacher J, et al.Dynamic control of enhancer activity drives stage-specific gene expression during flower morphogenesis[J].Nat Commun, 2019, 10(1): 1705.
[15] Javierre BM, Burren OS, Wilder SP, et al.Lineage-specific genome architecture links enhancers and non-coding disease variants to target gene promoters[J].Cell, 2016, 167(5): 1369-1384.
[16] Maurano MT, Humbert R, Rynes E, et al.Systematic localization of common disease-associated variation in regulatory DNA[J].Science, 2012, 337(6099): 1190-1195.
[17] Bai F, Shu P, Deng H, et al.A distal enhancer guides the negative selection of toxicglycoalkaloids during tomato domestication[J].Nat Commun, 2024, 15(1): 2894.
[18] Ma X, Mei S,Wuyun Q, et al.Super-enhancer-driven LncRNA PPARα-seRNA exacerbates glucolipid metabolism and diabetic cardiomyopathy via recruiting KDM4B[J].Mol Metab, 2024, 86: 101978.
[19] Trang KB,Pahl MC, Pippin JA, et al.3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity[J].medRxiv, 2024.
[20] Pan DZ,Garske KM, Alvarez M, et al.Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS[J].Nat Commun, 2018, 9(1): 1512.
[21] Qin Y, Grimm SA, Roberts JD, et al.Alterations in promoter interaction landscape and transcriptional network underlying metabolic adaptation to diet[J].Nat Commun, 2020, 11(1): 962.
[22] Jin L, Wang D, Zhang J, et al.Dynamic chromatin architecture of the porcine adipose tissues with weight gain and loss[J].Nat Commun, 2023, 14(1): 3457.
[23] Yan T, Yan N, Wang P, et al.Herbal drug discovery for the treatment of nonalcoholic fatty liver disease[J].Acta Pharm Sin B, 2020, 10(1): 3-18.
[24] Xu L, Yin L, Qi Y, et al.3D disorganization and rearrangement of genome provide insights into pathogenesis of NAFLD by integrated Hi-C,Nanopore, and RNA sequencing[J].Acta Pharm Sin B, 2021, 11(10): 3150-3164.
[25] Xue A, Wu Y, Zhu Z, et al.Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes[J].Nat Commun, 2018, 9(1): 2941.
[26] Greenwald WW,Chiou J, Yan J, et al.Pancreatic islet chromatin accessibility and conformation reveals distal enhancer networks of type 2 diabetes risk[J].Nat Commun, 2019, 10(1): 2078.
[27] Miguel-Escalada I, Bonàs-Guarch S, Cebola I, et al.Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes[J].Nat Genet, 2019, 51(7): 1137-1148.

染色质三维结构与基因调控网络在儿童代谢性疾病中的遗传学机制进展

Progress in genetic mechanisms of chromatin 3D structure and gene regulatory networks in pediatric metabolic disorders

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

[1]	李宇, 武庆斌. 乳糖在肠道的代谢与乳糖不耐受症[J]. 中国儿童保健杂志, 2025, 33(8): 813-816.
[2]	杨茜, 张婧洁, 石影, 刘艳敏, 张永花. 不同月龄婴儿血清25-羟维生素D与智力发育的相关性[J]. 中国儿童保健杂志, 2025, 33(8): 817-822.
[3]	王启文, 刘丹, 熊璐, 李诺, 张晶磊, 龚煜杰, 朱绍华, 朱元忠, 俞斌, 燕虹. 孕妇童年期忽视经历与子代出生体重的关系[J]. 中国儿童保健杂志, 2025, 33(8): 823-828.
[4]	王雪, 李智慧, 孔燕, 于桂玲. 基于行为改变轮理论的顺应喂养干预在6~12月龄婴儿及其照护者中的应用[J]. 中国儿童保健杂志, 2025, 33(8): 829-834.
[5]	达振强, 李婷婷, 南楠, 魏丽琼, 陈奕铭, 朱瑛, 高杨, 安旦旦, 张娜琪, 马昕, 郭金仙. 甘肃地区不同营养状况下骨龄提前的风险分析[J]. 中国儿童保健杂志, 2025, 33(8): 835-840.
[6]	许玥, 郜统勋, 胡思源, 李梅芳, 栾奕博, 许晨霞. ω-3/6多不饱和脂肪酸与儿童肥胖的两样本孟德尔随机化研究[J]. 中国儿童保健杂志, 2025, 33(8): 841-847.
[7]	徐娴, 宣佳乐, 王斌, 李娟, 刘世建, 余晓丹. 学龄期儿童抗生素暴露水平及影响因素[J]. 中国儿童保健杂志, 2025, 33(8): 848-853.
[8]	王文, 王喆, 蒋秀蕾, 姜妍琳, 胡英华, 王明月, 牟春笋, 王春香. 基于孟德尔随机化探讨肠道菌群及代谢通路与矮身材的因果关系[J]. 中国儿童保健杂志, 2025, 33(8): 854-859.
[9]	秦成洁, 陈月, 杨柳, 巫慧敏, 金晟娴, 梁燕, 任妍. 家庭婴幼儿照护质量评估量表的构建及信效度检验[J]. 中国儿童保健杂志, 2025, 33(8): 860-865.
[10]	赵惠茹, 宋陆陆, 张剑峰. 京津冀地区城市青少年健康素养状况及其与不良饮食行为的相关性[J]. 中国儿童保健杂志, 2025, 33(8): 866-870.
[11]	祝莹莹, 张子皓, 祝家元, 喻金枝, 丁晨莉, 黄铮. 家庭干预在儿童非器质性喂养困难管理中的应用[J]. 中国儿童保健杂志, 2025, 33(8): 871-877.
[12]	王烨妍, 王景刚, 郜莉, 郑浩轩, 陈永强, 曹建国. 儿童肥胖症运动干预研究进展[J]. 中国儿童保健杂志, 2025, 33(8): 878-882.
[13]	徐河, 支金草, 常庆, 王艳. 非侵入性迷走神经电刺激治疗注意缺陷多动障碍的潜在机制研究进展[J]. 中国儿童保健杂志, 2025, 33(8): 883-887.
[14]	王聪颖, 张梦楠, 成童, 张明明, 王宏茂, 张霆, 关宏岩, 李晓惠. 川崎病患儿疾病恢复早期身体活动水平评估[J]. 中国儿童保健杂志, 2025, 33(8): 888-892.
[15]	王宸, 吴维佳, 黄垂灿, 罗庆, 张春晖, 王平, 吴少晶, 樊利春. 不同照护者儿童青少年维生素D不足及缺乏的研究[J]. 中国儿童保健杂志, 2025, 33(8): 893-896.